Genetic analysis of iron citrate toxicity in yeast: Implications for mammalian iron homeostasis

被引:38
作者
Chen, OS [1 ]
Hemenway, S [1 ]
Kaplan, J [1 ]
机构
[1] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA
关键词
D O I
10.1073/pnas.232392299
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Deletion of the yeast homologue of frataxin, YFH1, results in mitochondrial iron accumulation and respiratory deficiency (petite formation). We used a genetic screen to identify mutants that modify iron-associated defects in respiratory activity in Deltayfh1 cells. A deletion in the peroxisomal citrate synthase CIT2 in Deltayfh1 cells decreased the rate of petite formation. Conversely, overexpression of CIT2 in Deltayfh1 cells increased the rate of respiratory loss. Citrate toxicity in Deltayfh1 cells was dependent on iron but was independent of mitochondrial respiration. Citrate toxicity was not restricted to iron-laden mitochondria but also occurred when iron accumulated in cytosol because of impaired vacuolar iron storage. These results suggest that high levels of citrate may promote iron-mediated tissue damage.
引用
收藏
页码:16922 / 16927
页数:6
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